The GROUP study will contribute to insight in risk and protective factors in the aetiology of non-affective psychotic disorders, and in the variation in their course and outcome.

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ObjectiveThis study aimed to assess the heterogeneity and stability of cognition in patients with a non‐affective psychotic disorder and their unaffected siblings. In addition, we aimed to predict the cognitive subtypes of siblings by their probands.MethodAssessments were conducted at baseline, 3 and 6 years in 1119 patients, 1059 siblings and 586 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study. Group‐based trajectory modeling was applied to identify trajectories and clustered multinomial logistic regression analysis was used for prediction modeling. A composite score of eight neurocognitive tests was used to measure cognitive performance.ResultsFive stable cognitive trajectories ranging from severely altered to high cognitive performance were identified in patients. Likewise, four stable trajectories ranging from moderately altered to high performance were found in siblings. Siblings had a higher risk of cognitive alteration when patients’ alteration was mild (OR = 2.21), moderate (OR = 5.70), and severe (OR = 10.07) compared with patients with intact cognitive function. The familial correlation coefficient between pairs of index patients and their siblings was 0.27 (P = 0.003).ConclusionsThe cognitive profiles identified in the current study might be suitable as endophenotypes and could be used in future genetic studies and predicting functional and clinical outcomes.

Unaffected siblings of patients with schizophrenia are heterogeneous with respect to cognitive function. The poorer the cognitive profile of the sibling, the higher the level of correspondence with the proband. The sibling's cognitive subtype was predictive for disease course in the proband. Distinguishing cognitive subtypes of unaffected siblings may be of relevance for genetic studies.

Cognitive functioning is a candidate intermediate phenotype given significant small to large alterations in patients and intermediate alterations in first-degree relatives.

(2012). Cannabis and cognitive performance in psychosis: a cross-sectional study in patients with non-affective psychotic illness and their unaffected siblings. Psychological Medicine, 42, pp 705-716 doi:10.1017/S0033291711001656 Background. The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings.Method. We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed.Results. Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d x0.20 to x0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning.Conclusions. Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.

Our results do not support the validity of schizophrenia subtypes. Schizophrenia can be distinguished from brief psychotic disorder and psychotic disorder not otherwise specified. These findings may fuel the actual DSM-V discussion.

Disease heterogeneity in patients with psychotic disorder may be explained by distinct profiles of premorbid adjustment. The current study explored premorbid adjustment profiles in patients with psychotic disorders, associations with cognitive and clinical characteristics after disease onset, and the role of familial factors. A total of 666 patients with psychosis (predominantly schizophrenia), 673 siblings, 575 parents, and 585 controls were included in this study. Cluster analyses were performed on the patients' scores of the Premorbid Adjustment Scale (PAS), using information on domains (social, academic) and age epochs (childhood, early adolescence, late adolescence). Resulting profiles were compared with characteristics in patients and their unaffected relatives. Six clusters, labeled normal, social intermediate, academic decline, overall decline, overall intermediate, and overall impaired adjustment, were identified in patients. Patients in different clusters differed from each other on cognitive, clinical, and functional characteristics after disease onset. Heterogeneity in the patient population may be explained in part by the adjustment profile prior to disease onset. This is in line with theories that propose different etiologies in the development of psychosis. Patient profiles were expressed in unaffected siblings, suggesting a role for familial factors.